Genotype and Phenotype Correlation in Hereditary Thrombotic Thrombocytopenic Purpura (Upshaw-Schulman Syndrome)

Summary

Hereditary thrombotic thrombocytopenic purpura (Upshaw-Schulman syndrome) is a rare disorder characterized by thrombocytopenia as a result of platelet consumption, microangiopathic hemolytic anemia, occlusion of the microvasculature with von Willebrand factor-platelet-thrombic and ischemic end organ damage. The underlying patho-mechanism is a severe congenital ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, 13) deficiency which is the result of compound heterozygous or homozygous ADAMTS13 gene mutations.

Although considered a monogenic disorder the clinical presentation in Upshaw-Schulman syndrome patients varies considerably without an apparent genotype-phenotype correlation. In 2006 we have initiated a registry for patients with Upshaw-Schulman syndrome and their family members to identify possible triggers of acute bouts of TTP, to document individual clinical courses and treatment requirements as well as possible side effects of long standing plasma substitution, e.g. alloantibody formation or viral infections.

Conditions

• Thrombotic Thrombocytopenic Purpura
• Congenital Thrombotic Thrombocytopenic Purpura
• Familial Thrombotic Thrombocytopenic Purpura
• Thrombotic Thrombocytopenic Purpura, Congenital
• Upshaw-Schulman Syndrome

Interventions

OTHER

Observation

No interventions planned: treatment of patients at the discretion of the treating/responsible physician

Sponsors & Collaborators

• Swiss National Science Foundation

  collaborator OTHER

• Mach Gaensslen Foundation

  collaborator OTHER

• Baxalta Innovations GmbH, Wien, Austria

  collaborator UNKNOWN

• Insel Gruppe AG, University Hospital Bern

  lead OTHER

Principal Investigators

• Johanna A Kremer Hovinga, MD · University Clinic of Hematology and Central Hematology Laboratory, Bern University Hospital and the University of Bern, Inselspital

• Bernhard Lämmle, M.D. · University Medical Center, Center for Thrombosis and Hemostasis, Mainz, Germany

• Yoshihiro Fujimura, M.D. · Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, Japan

• Ingrid Hrachovinova, Ph.D. · Institute of Hematology and Blood Transfusion, Coagulation Laboratory, Prague, Czech Republic

• Petter Quist-Paulsen, M.D., Ph.D. · Department of Hematology, St Olavs Hospital, 7006 Trondheim, Norway

• Reinhard Schneppenheim, M.D., Ph.D. · Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

• James N. George, MD · University of Oklahoma Health Sciences Center, Department of Medicine, United States of America

• Paul N Knoebl, MD · Medical University of Vienna, Div. Hematology and Hemostasis, Austria

Eligibility

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2006-10-31

Primary Completion

2030-10-31

Completion

2030-10-31

Countries

• United States
• Austria
• Czechia
• Germany
• Japan
• Norway
• Switzerland

Study Locations